Although social cognition dysfunction is a hallmark initial symptom of frontotemporal dementia (FTD) and schizophrenia, it has received relatively little systematic study in these disorders and the relationship between neurodegenerative and neuropsychiatric structural changes and brain activation patterns is only beginning to be explored. The primary goal of the proposed research is to use an integrated set of structural and functional MRI measures to define the anatomic and physiologic abnormalities underlying social cognition dysfunction in patients with frontotemporal dementia and schizophrenia with the further goal of improving the management and rehabilitation of these patients. In FTD and schizophrenia, quantitative volumetric MRI methods are capable of detecting differential neuroanatomic abnormality patters in relation to areas of cognitive dysfunction. Likewise, functional connectivity MRI (fcMRI) tools have revealed activity of specific regional brain networks associated with social cognition tasks. Therefore, our specific aims are (1) to develop an objective battery to assess social cognition in FTD and schizophrenia, (2) to investigate regional brain atrophy patterns associated with social cognitive impairment in patients with FTD and schizophrenia, and (3) to determine whether subtle social cognitive dysfunction is associated with functional abnormalities in brain networks associated with social cognition using resting-state functional MRI data and compare these findings to those related to regional atrophy patterns in FTD and schizophrenic patients. Across the neurodegenerative and neuropsychiatric diseases studied here, we hypothesize that social cognitive impairments will relate more to functional and structural abnormalities in networks subserving social cognition and less to diagnostic classification; that is, some patients with FTD or schizophrenia will have prominent social cognitive impairment and underlying brain abnormalities in networks subserving social cognition while some patients will have other types of symptoms with relative preservation of social cognition, supporting the recently conceived concept of common domains of cognitive-affective dysfunction across neuropsychiatric disorders. PUBLIC HEALTH RELEVANCE: Frontotemporal dementia (FTD) and schizophrenia are both devastating disorders; an early symptom in both disorders is impairment in abilities related to social and interpersonal behavior. It is not yet clear whether there are similar problems in both disorders. In this study, we aim to study social cognitive behavior and brain structure and function, predicting that we will find similar abnormalities in both conditions, which we hope will lay the foundation for better diagnosis and management techniques.